Brazilian research uncovers how liver nerves regulate glucose production under stress

Noradrenaline (also called norepinephrine) is a neurotransmitter that plays a key role in rapid responses to stress or danger, raising heart rate, blood pressure and the release of glucose from energy reserves. Most studies in the scientific literature regarding the regulation of glucose synthesis by the liver focus on the action of hormones in the pancreas and adrenal glands.

Luiz Carlos Navegantes, Professor, Department of Physiology at the University of São Paulo's Ribeirão Preto Medical School (FMRP-USP) and corresponding author of the articleThe originality of our study lies in showing that the central nervous system, via sympathetic nerves, can control CREB and activate de novo glucose production by the liver if extra energy is required. We describe the anatomy of the innervation in the liver using a methodology never used before in Brazil."

The researchers deployed a technique known as 3DISCO (three-dimensional imaging of solvent-cleared organs), a histology method that makes biological samples more transparent using organic solvents and produces a 3D image with the nerves clearly visible.

The other co-authors included researchers affiliated with the University of Oxford and Francis Crick Institute in the United Kingdom, and Marc Montminy at the Salk Institute for Biological Studies in the United States. The latter discovered CREB and elucidated its role in energy metabolism regulation, pointing to potential targets for drugs to combat insulin resistance, diabetes and obesity.

Methodology

The scientists used 3D immunoimaging to analyze the distribution of sympathetic nerves in the mouse liver, observing a dense innervation comprising thick primary nerve fibers with smaller branches that did not make direct contact with hepatocytes (liver cells).

To investigate the physiological role of this innervation, the mice were exposed to cold (4 °C) for up to six hours. Cold stress activated CREB/CRTC2 via calcium (Ca2+) signaling to assure the supply of glucose to muscles and keep the body warm.

Source:

São Paulo Research Foundation (FAPESP)

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